LIGAND-INDUCED INTERCONVERSION OF AFFINITY STATES IN MEMBRANE-BOUND ACETYLCHOLINE-RECEPTOR FROM TORPEDO-CALIFORNICA - EFFECTS OF SULFHYDRYL AND DISULFIDE REAGENTS

The nicotinic acetylcholine receptor from Torpedo californica, in membrane-bound form, can undergo conversion from a state(s) of low affinity to one(s) of high affinity for carbamylcholine upon pretreatment with this ligand. The involvement of disulfide bonds in this conformational transition is suggested since treatment with a reducing agent, dithiothreitol, prevents the conversion. In addition treatment with p-chloromercuribenzoate similarly blocks the conversion to high affinity state(s) by the cholinergic ligand, while other reagents such as iodoacetic acid or iodoacetamide do not. These results suggest the possible involvement of sulfhydryl groups in the transition. Unmodified acetylcholine receptor in the high-affinity form(s) induced by carbamylcholine can revert to a form(s) of low affinity upon removal of the ligand. However, treatment with p-chloromercuribenzoate prior to such removal prevents the system from reverting to low affinity after removal of carbamylcholine. Those results again suggest that sulfhydryl groups may be important for the conformational transitions responsible for interconversion of affinity states of the receptor. They are also indicative of the possibility of stabilizing states of the receptor complex which should be useful for studies of its mechanism, and they suggest a possible chemical base for the conformational transitions. © 1979, American Chemical Society. All rights reserved.